Liposomal solubilization

Deo, N. and Somasundaran, P, Mechanism of mixed liposome solubilization in the presence of sodium dodecyl sulfate. Colloids Surfactants 186 33-41, 2001. 

Liposomal solubilization is an effective approach for the delivery of potent, insoluble drug candidates. However, careful consideration of the various lipid and drug properties along with an emphasis on manufacturing conditions is needed for the successful development of a marketable formulation. 

In light of the information presented, it appears that liposomes have much to offer as an improved delivery system for inhaled bronchodilators as they can provide sustained release, solubilization, stability, and safety in an inhalable formulation. 

Van Bloois, L., Dekker, D. D., and Crommelin, D. J. A. (1987). Solubilization of lipophilic drugs by amphiphiles Improvement of the apparent solubility of almitrine bismesylate by liposomes, mixed micelles and O/W emulsions, Acta Pharmaceut. TechnoL,... 

Weiner, A. L. (1987). Lamellar systems for drug solubilization, in Liposomes From Biophysics to Therapeutics (M. J. Ostro, ed.), Marcel Dekker, New York, pp. 339-369. 

Solubilization of an active H,K-ATPase is also a prerequisite for reconstitution of the enzyme into liposomes. With these H,K-ATPase proteoliposomes it is then possible to study the transport characteristics of pure H,K-ATPase, without the interference of residual protein contamination that is usually present in native vesicular H,K-ATPase preparations. Rabon et al. [118] first reported the reconstitution of choleate or n-octylglucoside solubilized H,K-ATPase into phosphatidylcholine-cholesterol liposomes. The enzyme was reconstituted asymmetrically into the proteoliposomes with 70% of the pump molecules having the cytoplasmic side extravesicular. In the presence of intravesicular K, the proteoliposomes exhibited an Mg-ATP-dependent H transport, as monitored by acridine orange fluorescence quenching. Moreover, as seen with native H,K-ATPase vesicles, reconstituted H,K-... 

ATPase also catalyzed a passive Rb -Rb exchange, the rate of which was comparable to the rate of active Rb efflux. This suggested that the K-transporting step of H,K-ATPase is not severely limited by a K -occluded enzyme form, as was observed for Na,K-ATPase. Skrabanja et al. [164] also described the reconstitution of choleate solubilized H,K-ATPase into phosphatidylcholine-cholesterol liposomes. With the use of a pH electrode to measure the rate of H transport they observed not only an active transport, which is dependent on intravesicular K, but also a passive H exchange. This passive transport process, which exhibited a maximal rate of 5% of the active transport process, could be inhibited by vanadate and the specific inhibitor omeprazole, giving evidence that it is a function of gastric H,K-ATPase. The same authors demonstrated, by separation of non-incorporated H,K-ATPase from reconstituted H,K-ATPase on a sucrose gradient, that H,K-ATPase transports two protons and two ions per hydrolyzed ATP [112]. 

Once the desired mixture of lipid components is dissolved and homogenized in organic solvent, one of several techniques may be used to disperse the liposomes in aqueous solution. These methods may be broadly classified as (1) mechanical dispersion, (2) detergent-assisted solubilization, and (3) solvent-mediated dispersion. 

Krogh-Hansen U, LeMarie M, Moller JV. The mechanism of detergent solubilization of liposomes and protein-containing membranes. Biophys J 1998 75 2932-2941. 

DNA and/or protein vaccine entrapment in DRV liposomes is monitored by measuring the vaccine in the suspended pellet and combined supernatants. The most convenient way to monitor DNA entrapment is by using radio-labelled or DNA. For protein entrapment, the use of I-labelled protein tracer is recommended. If a radiolabel is not available or cannot be used, appropriate quantitative techniques should be employed. To determine DNA or protein by such techniques, a sample of the liposome suspension is mixed with Triton X-100 (up to 5% final concentration) or, preferably, with isopropanol (1 1 volume ratio) so as to liberate the entrapped materials. However, if Triton X-100 or the solubilized liposomal lipids interfere with the assay of the materials, liposomal lipids or the DNA must be extracted using appropriate techniques (6). Entrapment values for protein and DNA, whether alone or coentrapped, range between about 20% to 80% (protein) and 30%i to 100%i (DNA) of the initial material depending on the DNA or protein used and, in the case of DNA, the presence or absence of cationic charge. Values are highest for DNA when it is entrapped into cationic DRV (typical values in Table 1). 

The polar character of the liposomal core makes the encapsulation of polar drug molecules possible. Amphiphilic and lipophilic molecules are solubilized within the phospholipid bilayer according to their affinity toward the phospholipids. Participation of nonionic surfactants instead of phospholipids in the bilayer formation results in Niosomes . The term sphingosomes is suggested for vesicles from sphingolipids. However, the nomenclature is not consistent, and the term liposomes is used as a general term, although vesicles would be the better choice. 

Phospholipids, when dispersed in water, may exhibit self-assembly properties (either as micellar self-assembly aggregates or larger structures). This may lead to aggregates that are called liposomes or vesicles. Liposomes are structures that are empty cells and that are currently being used by some industries. They are microscopic vesicles or containers formed by the membrane alone, and are widely used in the pharmaceutical and cosmetic fields because it is possible to insert chemicals inside them. Liposomes may also be used solubilize (in its hydrophobic part) hydro-phobic chemicals (water-insoluble organic compounds) such as oily substances so that they can be dispersed in an aqueous medium by virtue of the hydrophilic properties of the liposomes (in the alkyl region). 

During the past decades, liposomes have been used for drug delivery on account of their unique solubilization characteristics for water-insoluble organic substances. A liposome encapsulates a region of aqueous solution inside a hydrophobic membrane dissolved hydrophilic solutes cannot readily pass through the lipids. Hydrophobic chemicals can be dissolved into the membrane, and this way, the liposome can carry... 

Part II starts with the possibilities of ACE for characterizing the relevant physicochemical properties of drugs such as lipophilicity/hydrophilicity as well as thermodynamic parameters such as enthalpy of solubilization. This part also characterizes interactions between pharmaceutical excipients such as amphiphilic substances (below CMC) and cyclodextrins, which are of interest for influencing the bioavailability of drugs from pharmaceutical formulations. The same holds for interactions of drugs with pharmaceutical vehicle systems such as micelles, microemulsions, and liposomes. 

Formulation of Insoluble Compounds, Liposomes in Solubilization, Micellization and Drug Solubility Enhancement, and Polymeric Micelles in V Mer-lnsoluble Drug Delivery. ... 

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